※ PPS INTRODUCTION:

Recently, an interesting and important
question has emerged from feedbacks of experimentalists.
Frequently, experimental researchers prefer to study novel
PTM sites to elucidate new functions. Thus, it's important
to show whether there have been any sites experimentally
verified as real PTM sites in given proteins. And such
information will be greatly useful for researchers to
avoid reduplicate work. Although we and other bioinformatists
developed numerous tools for PTM sites prediction, these
softwares could only regard prediction results as potentially
real sites. Currently, several public databases, e.g.,
Phospho.ELM
(Diella,
et al., 2004; Diella,
et al., 2008) and UniProt (Boutet,
et al., 2007), have been developed to contain
PTM information of proteins. However, these annotations
are usually not integrated. Moreover, due to the diversity
and heterogeneity of protein names, it's difficult to
fully obtain the known PTM information for a given protein,
by database searching.

In this work, we developed a novel software of PTMs
Peptide Scanner (PPS), to
reveal known or highly potential PTM sites in eukaryotic
proteins. Five typical PTMs were considered, including
phosphorylation, sumoylation, palmitoylation, methylation
and acetylation. And the experimentally verified PTM sites
were taken from Phospho.ELM
7.0 (Diella,
et al., 2004; Diella,
et al., 2008) and our previous studies (Chen,
et al., 2006; Li,
et al., 2006; Ren,
et al., 2008; Xue,
et al., 2006; Xue,
et al., 2006; Zhou,
et al., 2006), containing 18 179 known sites.
Based on our previous hypothesis of similar peptides with
potentially similar functions, we designed a straightforward
approach of conserved peptide matching (CPM) algorithm.
Given a protein sequence as input, PPS will compare it
to the experimentally verified PTMs peptides to find the
identical or highly conserved hits. The identical hits
might be bona fide modified peptides in experimentally
verified proteins or conserved in their highly similar
homologs. Thus, PPS could be useful for annotation of
covalent modifications information across eukaryotes.
As an application, we computationally revealed 71 663
identical hits in six eukaryotic organisms, including
H. sapiens, M. musculus, D. melanogaster,
C. elegans, S. pombe, and S. cerevisiae.
Obviously, most of these results could be highly potential
PTM sites and greatly helpful for further experimental
verification. Furthermore, highly conserved hits might
also point to potentially conserved modifications. In
our results, there were 7 911 highly potential PTM hits
(with ≤3 conservative substitutions) found in the six
eukaryotes. In addition, we carried out a proteome-wide
study of creation or disruption of covalent modification
sites by alternative splicing (AS) in H. sapiens.
Taken together, we proposed PPS could be a multiple useful
tool for PTM sites analyses. Finally, the online service
and local packages of PPS 1.0 were implemented in JAVA
1.5.